Development of a nanoporous and multilayer drug-delivery platform for medical implants.

Biodegradable polymers can be applied to a variety of implants for controlled and local drug delivery. The aim of this study is to develop a biodegradable and nanoporous polymeric platform for a wide spectrum of drug-eluting implants with special focus on stent-coating applications. It was synthesized by poly(DL-lactide-co-glycolide) (PLGA 65:35, PLGA 75:25) and polycaprolactone (PCL) in a multilayer configuration by means of a spin-coating technique. The antiplatelet drug dipyridamole was loaded into the surface nanopores of the platform. Surface characterization was made by atomic force microscopy (AFM) and spectroscopic ellipsometry (SE). Platelet adhesion and drug-release kinetic studies were then carried out. The study revealed that the multilayer films are highly nanoporous, whereas the single layers of PLGA are atomically smooth and spherulites are formed in PCL. Their nanoporosity (pore diameter, depth, density, surface roughness) can be tailored by tuning the growth parameters (eg, spinning speed, polymer concentration), essential for drug-delivery performance. The origin of pore formation may be attributed to the phase separation of polymer blends via the spinodal decomposition mechanism. SE studies revealed the structural characteristics, film thickness, and optical properties even of the single layers in the triple-layer construct, providing substantial information for drug loading and complement AFM findings. Platelet adhesion studies showed that the dipyridamole-loaded coatings inhibit platelet aggregation that is a prerequisite for clotting. Finally, the films exhibited sustained release profiles of dipyridamole over 70 days. These results indicate that the current multilayer phase therapeutic approach constitutes an effective drug-delivery platform for drug-eluting implants and especially for cardiovascular stent applications.

The nonlinear heat release response of stratified lean-premixed flames to acoustic velocity oscillations

This paper analyzes the forced response of swirl-stabilized lean-premixed flames to high-amplitude acoustic forcing in a laboratory-scale stratified burner operated with CH4 and air at atmospheric pressure. The double-swirler, double-channel annular burner was specially designed to generate high-amplitude acoustic velocity oscillations and a radial equivalence ratio gradient at the inlet of the combustion chamber. Temporal oscillations of equivalence ratio along the axial direction are dissipated over a long distance, and therefore the effects of time-varying fuel/air ratio on the response are not considered in the present investigation. Simultaneous measurements of inlet velocity and heat release rate oscillations were made using a constant temperature anemometer and photomultiplier tubes with narrow-band OH*/CH* interference filters. Time-averaged and phase-synchronized CH* chemiluminescence intensities were measured using an intensified CCD camera. The measurements show that flame stabilization mechanisms vary depending on equivalence ratio gradients for a constant global equivalence ratio (φg=0.60). Under uniformly premixed conditions, an enveloped M-shaped flame is observed. In contrast, under stratified conditions, a dihedral V-flame and a toroidal detached flame develop in the outer stream and inner stream fuel enrichment cases, respectively. The modification of the stabilization mechanism has a significant impact on the nonlinear response of stratified flames to high-amplitude acoustic forcing (u'/U∼0.45 and f=60, 160Hz). Outer stream enrichment tends to improve the flame's stiffness with respect to incident acoustic/vortical disturbances, whereas inner stream stratification tends to enhance the nonlinear flame dynamics, as manifested by the complex interaction between the swirl flame and large-scale coherent vortices with different length scales and shedding points. It was found that the behavior of the measured flame describing functions (FDF), which depend on radial fuel stratification, are well correlated with previous measurements of the intensity of self-excited combustion instabilities in the stratified swirl burner. The results presented in this paper provide insight into the impact of nonuniform reactant stoichiometry on combustion instabilities, its effect on flame location and the interaction with unsteady flow structures. © 2011 The Combustion Institute.

Evaluation of the functionality of biodegradable polymeric platforms for drug delivery systems

We present the development of a drug-loaded triple-layer platform consisting of thin film biodegradable polymers, in a properly designed form for the desired gradual degradation. Poly(dl-lactide-co-glycolide) (PLGA (65:35), PLGA (75:25)) and polycaprolactone (PCL) were grown by spin coating technique, to synthesize the platforms with the order PCL/PLGA (75:25)/PLGA (65:35) that determine their degradation rates. The outer PLGA (65:35) layer was loaded with dipyridamole, an antiplatelet drug. Spectroscopic ellipsometry (SE) in the Vis-far UV range was used to determine the nanostructure, as well as the content of the incorporated drug in the as-grown platforms. In situ and real-time SE measurements were carried out using a liquid cell for the dynamic evaluation of the fibrinogen and albumin protein adsorption processes. Atomic force microscopy studies justified the SE results concerning the nanopores formation in the polymeric platforms, and the dominant adsorption mechanisms of the proteins, which were defined by the drug incorporation in the platforms. © 2013 Elsevier B.V. All rights reserved.